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Published on: July 18, 2025
Phage PM16 Therapy Induce Long-Term Protective Immunity Against Proteus mirabilis via Macrophage Priming
Lina Al Allaf1, Anton V Chechushkov1, Vera V Morozova1
1Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
Abstract:
Bacteriophages, traditionally viewed solely as antibacterial agents, are increasingly being studied for their immunomodulatory properties. In this study, we demonstrate that PM16 phage therapy not only effectively controls subcutaneous Proteus mirabilis infection in mice but also induces long-term specific humoral immunity against subsequent reinfection. This immunomodulatory effect was dose-dependent. In vitro, PM16 directly activates macrophages, leading to increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and inducible nitric oxide synthase, and enhances macrophage bactericidal activity against P. mirabilis. We assume that the enhancement of the adaptive immune response is mediated not by the phage acting as a classical antigenic adjuvant but by its ability to prime innate immune cells, specifically macrophages. This priming leads to more efficient bacterial clearance, antigen presentation, and the formation of protective immunological memory.
Insights
Bacteriophage therapy with PM16 controls Proteus mirabilis infections and enhances long-term immunity by activating macrophages. This phage therapy primes innate immunity, improving bacterial clearance and immunological memory.
Area of Science:
- Immunology
- Microbiology
- Bacteriophage Therapy
Background:
- Bacteriophages are increasingly recognized for immunomodulatory roles beyond antibacterial action.
- Understanding phage-host interactions is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the immunomodulatory effects of PM16 bacteriophage therapy against Proteus mirabilis infection.
- To explore the mechanisms underlying phage-induced adaptive immune responses.
Main Methods:
- Subcutaneous P. mirabilis infection model in mice treated with PM16 phage.
- In vitro assessment of macrophage activation, cytokine production, and bactericidal activity.
- Dose-response evaluation of phage therapy efficacy and immunogenicity.
Main Results:
- PM16 phage therapy effectively controlled P. mirabilis infection and induced long-term specific humoral immunity.
- Phage treatment dose-dependently enhanced macrophage activation, leading to increased pro-inflammatory cytokine and nitric oxide synthase production.
- Activated macrophages exhibited enhanced bactericidal activity against P. mirabilis.
Conclusions:
- PM16 bacteriophages possess significant immunomodulatory properties.
- Phage-induced immune enhancement is mediated by macrophage priming, improving bacterial clearance and adaptive immunity.
- This study highlights bacteriophages as potential agents for stimulating protective immunological memory.
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